Apparatus for purifying blood

ABSTRACT

Apparatus for purifying blood comprises a vessel containing one or more chambers arranged in series and containing micro-beads which enclose adsorbents and reagents for purifying blood. The vessel also includes a stator cavity which contains a pump rotor, preferably driven by an external rotary magnet. Means for agitating the beads in the chamber preferably consist of vanes connected to the pump rotor. In a preferred arrangement of the apparatus, the beads in a first chamber nearest the inlet contain urease and a cation-exchange resin in the sodium state, the beads of the second chamber contain activated charcoal and an exchange resin in the hydrogen state, and the beads of the third chamber contain an anion-exchange resin in the OH state.

United States Patent Meunier et al.

APPARATUS FOR PURIFYING BLOOD Rene Louise Meunier, Paris; Monique AdeleMarmonier, Lyon, both of France Inventors:

Sertna, Societe dEtudes Et De Recherches De Techniques NouvellesAppliquees S.A.

Filed: Dec. 3, 1969 Appl. No.: 881,800

Assignee:

Foreign Application Priority Data Dec. 3, 1969 France ..176342References Cited UNITED STATES PATENTS 9/1966 Canterbury ..210/416 X7/1970 Chang i...210/22 X 7/1965 Neuville ..259/66 X 1 1/1965 I-Iershler..259/DIG. 46

May 23, 1972 OTHER PUBLICATIONS Chang, T. M. S., Transactions AmericanSoc. For Artificial internal Organs, Vol. 12, 1966 pp. 13- 18 PrimaryExaminer-Samih N. Zaharna Att0rney-Breitenfeld & Levine [5 7] ABSTRACTApparatus for purifying blood comprises a vessel containing one or morechambers arranged in series and containing micro-beads which encloseadsorbents and reagents for purifying blood. The vessel also includes astator cavity which contains a pump rotor, preferably driven by anexternal rotary magnet. Means for agitating the beads in the chamberpreferably consist of vanes connected to the pump rotor. In a preferredarrangement of the apparatus, the beads in a first chamber nearest theinlet contain urease and a cationexchange resin in the sodium state, thebeads of the second chamber contain activated charcoal and an exchangeresin in the hydrogen state, and the beads of the third chamber containan anion-exchange resin in the OH state.

5 Claims, 1 Drawing Figure PATENTED MAY 2 3 1912 REA/5'5 J. L. MswwenMoNIQuE A. MHKMON/ER H11 oz/vevs APPARATUS FOR PURIFYING BLOOD Thepresent invention relates to various improvements in apparatus intendedfor renal purification knownas artificial kidenys, with the particularobject of appreciably reducing the size of the apparatus while retainingits efficiency.

It is known that purifying apparatus of conventional type involves thedialysis of blood flowing across sheets of cellophane placed either onrotary drums or on flat sheets. The need to ensure a sufficient exchangerate makes it necessary to provide a large surface, amounting to severalsquare meters, which greatly increases the cost and the dimensions ofthe apparatus, and makes it quite incapable of being moved about andusable only in hospital surroundings.

The invention is essentially based on the realization that it ispossible to reduce the dimensions of such apparatus appreciably, bymaking use of the properties possessed by certain polymers which can beformed as beads or micro-beads of a diameter varying between 5 and 100microns the walls of which being relatively thin and made in particularfrom nylon, collodion or silicone, permit physico-chemical exchange withthe surrounding medium, provided these beads contain within themsuitable physical, chemical; or biological reagents. The value of thesebeads of very small diameter resides in their spherical shape whichensures that they have a good mechanical resistance and gives them avery large exchange surface for a given volume.

Thus, by way of example, beads of 20 microns mean diameter have anexchange surface of 25 dm per milliliter, which for l ml of beads offersan exchange surface of 2.5 m corresponding to the dialyzer surface of aconventional artificial kidney.

It has been shown by T.M.S. Chang (Canadian Journal of Physiology andPharmacology, 44,115 1965) that it .is possible to prepare such beads,of a diameter between 0.005 and 5 mm, containing in their internalcavity various biological, physico-chemical or chemical reagents, bytechniques known in the art.

In the case of beads intended for renal purification of urea andnitrogenous residues, such as uric acid and creatinine, it has beensuggested that reagents capable of absorbing urea or of destroying it byenzyme action might be used. However, the adsorbents at present knownhave only a small capacity as regards urea, while the urease capable ofdestroying it by an enzymatic process involved the evolution of largequantities of ammonia. Various authors, for example, T.M.S. Chang(Trans. Amer. Soc. Artificial internal. Organ, l2l3, 1966) and SN.Levine (J. Biomed. Material Research I 375, [967) have suggested thatthe ammonia thus formed could be absorbed on a cation exchange resinlocated in the interior of the capsules. Unfortunately the fixing of theammonia on the resin results in the liberation of large quantities ofsodium or potassium, which are particularly undesirable.

This is why one of the important features of the present invention isthe avoidance of this disadvantage by making use of other cation andanion exchange resins capable of fixing the undesirable intennediateproducts and yielding only water at the final stage.

In accordance with another preferred feature of the invention aplurality of different exchange resins is employed in a purifying vesselcomprising a plurality of separate, suitably arranged chambers havingdifferent functions such that the fix ing reactions may take place in apredetermined sequence.

In a practical and particularly simple embodiment of the invention thereis used a purifying vessel comprising adsorbent materials, moreespecially activated charcoal, contained within the interior of thebeads and capable of fixing urea, uric acid and creatinine. However, thecapacity of these absorbents is limited and it is advantageous toperform periodically, with the same apparatus, an elution with water ofphysiological water of the compounds fixed on the adsorbent.

In accordance with another preferred feature of the invention systematicagitation of the purifying beads is effected within the vessel in suchmanner as to increase their exchange.

capacity within the medium of the blood to be purified. This iseffected, either'by using mechanical stirring with the aid of stirrersdriven through the intermediary of magnets, or by incorporating in thebeads a magnetic material, for example particles of magnetic ceramicmaterial, and subjecting them to the action of a magnetic field which isvariable in intensity and direction and is produced, for example, by anelectric current.

Finally, in order to eliminate any source of external contaminationthere is incorporated in the vessel, in accordance with the invention, acirculating pump, preferably driven by a magnetic field whereby anydriving connection between the interior and the exterior is avoided.Among compatible materials certain plastics materials such aspolycarbonates readily enable such an apparatus to be constructed, butthe choice of materials is not in any way restricted to polycarbonates.

One or more apparatus or purifying vessels according to the inventionmay be used along or conjointly with dialysis apparatus, so as to reducethe space occupied while retaining the efficiency.

The following description and the accompanying drawing enable the mannerin which the invention is performed to be better understood.

The accompanying drawing illustrates in axial section a purifying vesselaccording to the invention in a practical form comprising separatespecialized chambers successively transversed by the blood to bepurified.

The vessel 1, which is in the form of a hollow cylinder, is made from acompatible plastics material, for example, a polycarbonate, its interiorsurface being advantageously treated with an anti-coagulant. In theinterior of the hollow vessel, shown in the drawing in verticalposition, are formed successively three chambers 2, 3 and 4 and an uppercavity 5, the chamber 2 being bounded by the bottom wall 1a and aperforated inner partition 6, the chamber 3 by the perforated par tition6 and a similar perforated partition 7 the chamber 4 by the partition 7and a partition 8, the upper cavity 5 by the partition 8 and the upperend wall 1b of the vessel 1. The perforations in the partitions 6, 7 and8 permit passage of fluid from the chamber 2 to the chamber 3 and fromthe chamber 3 to the chamber 4. The base 10 has an opening 9 for theadmission of blood to be purified, connected to a supply pipe 9a.

Furthermore, an opening 10 in the partition 8 provides communicationbetween the chamber 4 and the cavity 5. Finally, the cavity 5communicates with the exterior by way of an outlet opening 11 connectedto an outlet pipe 1 la.

Each of the chambers 2, 3 and 4 is intended to receive purifying beadsof specialized function, the volume of these beads in a state of restbeing such as to establish the levels 2a, 3a and 4a respectively in thechambers.

The blood to be purified, entering the cartridge 1 through the inletopening 9 and leaving through the outlet opening 1 1, passes from onechamber to the next, and then into the cavity 5. In order that thepurifying beads may not leave their respective chambers, there isprovided on the mouth of the opening 9, in the chamber 2, on theperforations of the partition 6, on the perforations of the partition 7,and on the inlet side of the opening 10 thin porous plates or the like,l2, l3, l4, 15 respectively, for example plates of nylon.

In accordance with an essential feature of the invention the cavity 5constitutes the stator of a pump incorporated in the vessel and for thispurpose contains a rotor 20 rotatable amout the axis AA of thecylindrical vessel and producing within the vessel suction tending todraw the liquid from the vessel through the opening 10 and drive it outthrough the opening 11. The rotor 20 is, for example, a vaned or bladedrotor of 7 known type.

Actuation of the rotor is preferably effected by incorporating in itscentral part a permanent magnet 20a (driven magnet) and at the exteriorof the cartridge 1 on the other side of the wall 1b is arranged adriving magnet 21 rotatable about the axis AA. Rotation of magnet 21 maybe effected, for example, by a micro-motor, but it is the magneticcoupling between 21 and 20a that causes the rotation of the rotor 20which actuates the pump.

With the rotor 20 is associated a driving shaft 22 extending through thechambers of the vessel on the axis thereof. The whole of the assembly20,22 is mounted on two pivots 23, 24 cooperating respectively with thewalls la and lb.

In each of the chambers 2, 3, 4 the shaft 22 is associated with stirringvanes 25, 26, 27 arranged in each chamber above the level of thepurifying beads when in a state of rest.

Finally, the cartridge may comprise multiway inlet and outlet valves topermit the taking of samples and/or elution.

With the structure described above, the operation of the purifyingvessel is easy to understand. The rotor 20 driving the shaft 22 being inmotion the blood to be purified enters the vessel at 9 and leaves at l 1after passing through each individual chamber, the purifying beads beingwell distributed in each chamber by the stirring vanes.

Of course, the manner of driving the rotor 20 that has been described isonly one preferred example of a way of driving it without the passage ofdriving means through a wall; other conventional methods could be used.The same applies to the location of the pump in the vessel assembly.Similarly, the stirring of the beads could be efiected, without goingoutside the scope of the invention, by incorporating in them a certainnumber of beads of magnetic material of the same volume, theseadditional beads being driven by an external movable magnet, or moregenerally by any external device capable of creating a variable magneticfield. Finally, according to the method of purifying selected, one or aplurality of chambers may be used.

Some examples of purification will now be given, wherein use is made ofa vessel according to the invention.

EXAMPLE 1 In this case there is used a vessel having three chambers eachof which has a volume of about 100 ml.

The first chamber that the blood to be purified enters contains 50 ml ofnylon beads of 20 microns diameter, in accordance with the Changtechnique, containing urease for decomposing urea and a cation-exchangeresin, for the purpose of fixing the ammonia thus formed, the resinbeing in the sodium state.

The second chamber, into which the partially purified blood penetratescontains 50 ml of beads enclosing activated charcoal capable of fixinguric acid and creatinine, as well as an exchange resin in the hydrogenstate for fixing the excess of sodium resulting from the fixation ofammonia in the preceding stage.

Finally, the hydrochloric acid formed in the course of the second stageis fixed in the third chamber by means of 50 ml of beads containing ananion-exchange resin in the OH state which fixes the chlorine ion andforms water.

EXAMPLE 2 In this example there is used a vessel of the type defined,with a single chamber of volume of about 200 ml.

This chamber is provided with a mixture constituted by 150 ml of beadsof silicone containing particles of activated charcoal of mean diameter20 microns adapted to fix urea, uric acid and creatinine, and ml ofbeads of polystyrene containing particles of magnetic ceramic materialof 50 microns diameter.

The inlet and outlet pipes are provided with two-way or multiway valvesthat permit the introduction of solutions for washing the beads and forperiodic elution of the urea adsorbed by the charcoal, a particularlyactive solvent being physiological serum. Furthermore, the vessel isprovided with an external electrically conductive winding through whichis passed an electric current of sufficient intensity to effect movementof the beads containing the magnetic material, which by their movemententrain the beads containing the activated charcoal, thereby increasingtheir capacit for exchange. This apparatus has been tested on a dog of 3kg in which the blood urea count amounted, after perfusion with urea to4.26 g. per liter of blood.

Purification was effected at a speed of 50 ml per minute for 15 minutes,followed by elution with sterile water at a speed of ml/minute for thesame period.

This sequence of operations, carried out for 210 minutes, enabled theblood urea count of the animal to be brought to 0.55 g. per liter.

Among other modifications which may be made, the vessel according to theinvention may include auxiliary heating means such that the temperatureof the blood that passes through it may be kept at the physiologicaltemperature; for example the vessel may be enclosed by a skirt, thespace between the skirt and the cartridge serving for the circulation ofa heating liquid.

We claim:

1. Apparatus including a replaceable cartridge for purifying blood,comprising:

a. a cartridge housing having an inlet for connection to a source ofblood to be purified and an outlet for connection to a receiver ofpurified blood,

b. an impeller cavity and at least one chamber within said housingbetween said'inlet and outlet, said cavity and chamber communicatingwith each other,

e. blood-purifying beads partially filling said chamber,

d. a vane within said chamber for agitating said beads while blood flowsthrough said chamber,

e. a pump impeller rotatably mounted within said impeller cavity, andmeans connecting said vane to said impeller so that said vane rotateswith said impeller,

f. a drive motor external to said housing, and

g. separable coupling means for transmitting rotary motion from saidmotor to said impeller for causing the latter to pump blood from saidinlet, through said chamber and impeller cavity, and out said outlet,whereby said cartridge may be separated from said motor and blood sourceand receiver and replaced with another similar cartridge.

2. A cartridge as defined in claim 1 wherein said separable couplingincludes a magnet within said cavity connected to said impeller, and acooperating magnet outside said housing driven by said motor.

3. A cartridge as defined in claim 1 wherein said beside havemicro-membrane walls enclosing an adsorbent.

4. A cartridge as defined in claim 3 wherein said adsorbent is activatedcharcoal.

5. A cartridge as defined in claim 1 including three chambers arrangedin series within said housing, and wherein said beads havemicro-membrane walls enclosing reagents for purifying blood, said beadsin the chamber nearest said inlet containing urease and acation-exchange resin in the sodium state, the beads in the nextsucceeding chamber containing activated charcoal and an exchange resinin the hydrogen state, and the beads in the chamber closest said outletcontaining an anion-exchange resin in the OH state.

2. A cartridge as defined in claim 1 wherein said separable couplingincludes a magnet within said cavity connected to said impeller, and acooperating magnet outside said housing driven by said motor.
 3. Acartridge as defined in claim 1 wherein said beside have micro-membranewalls enclosing an adsorbent.
 4. A cartridge as defined in claim 3wherein said adsorbent is activated charcoal.
 5. A cartridge as definedin claim 1 including three chambers arranged in series within saidhousing, and wherein said beads have micro-membrane walls enclosingreagents for purifying blood, said beads in the chamber nearest saidinlet containing urease and a cation-exchange resin in the sodium state,the beads in the next succeeding chamber containing activated charcoaland an exchange resin in the hydrogen state, and the beads in thechamber closest said outlet containing an anion-exchange resin in the OHstate.